The long term aims of this project are to: 1) understand the effect of varying degrees and levels of SCI and dysfunction (SCI/D) on female sexual response: 2) identify the specific neuronal pathways involved in female sexual responses; and 3) develop and evaluate new assessment and treatment methods for neurogenic sexual dysfunction in women. In this project, we plan to build upon our findings in women with SCI to study sexual response in human females with SCD secondary to multiple sclerosis (MS). We will study sexual arousal and orgasm in women with MS to see if similar effects as in women with SCIs can be documented based upon the extent and location of their SCD. We will provide anatomical confirmation of our human findings by studying the urethrogenital (UG) reflex model, a spinal sexual reflex and vaginal changes in the rat. We will study rats that are intact, with bilateral hypogastric, pelvic and pudendal nerve cuts in order to determine the contribution of the sympathetic, parasympathetic and somatic nervous system in regulating genital arousal and orgasm. Peripheral and brain stimulation will be performed in order to mimic peripheral and psychogenic sexual stimulation. We will also test the effects of pharmacologic manipulation of the sympathetic nervous system (SNS) on sexual arousal in women with SCD and will test two treatment protocols aimed at retraining reflex orgasm in women with neurogenic FSD. Our central hypotheses are: 1) In females, the SNS regulates psychogenic genital vasocongestion 2) In females the orgasmic reflex requires the presence of an intact sacral spinal cord 3) In females a pattern generator is responsible for the orgasmic reflex 4) In females with SCIID and preserved sympathetic innervation to the genitals, pharmacologic sympathetic manipulation will alter genital responsiveness and 5) In females with neurogenic sexual dysfunction of spinal etiology use of a clitoral vacuum pump and vibratory stimulation will improve orgasmic ability. This grant represents a new collaborative effort between a long-standing research team led by physiatrist and a basic scientist, all with extensive experience studying female sexual response after neurologic lesions. These studies will provide information about the expected impact of SCD on female sexual response along with anatomical confirmation of the findings in the rat and test three treatment protocols for neurogenic sexual dysfunction.